Clopidogrel Resistance in Neurovascular Stenting: Correlations between Light Transmission Aggregometry,VerifyNow, and the Multiplate

BACKGROUND AND PURPOSE:Clopidogrel resistance is blamed for thromboembolic complications in neurovascular stent placement. Platelet-function assays are weakly standardized. The aim of this study was to correlate the results of 3 different platelet-inhibition measurements (from light transmission aggregometry, the VerifyNow P2Y12 test, and the Multiplate analyzer) and their relation to periprocedural thromboembolic complications in elective neurovascular stent placement.MATERIALS AND METHODS:Clopidogrel resistance was determined on the day of the intervention according to predefined platelet reactivity cutoff values. All 3 tests were performed in 103 consecutive neurovascular stent-placement procedures in 97 patients (extracranial, n = 77; intracranial, n = 26).RESULTS:The clopidogrel resistance rates were 47.6% (light transmission aggregometry), 50.5% (VerifyNow), and 35.9% (Multiplate). In 67% of the patients, clopidogrel resistance was present according to at least one method. The correlations of qualitative results that classified a patient as responsive or resistant to clopidogrel were 67.9% for light transmission aggregometry with VerifyNow, 77.7% for light transmission aggregometry with the Multiplate, and 66% for VerifyNow with the Multiplate. Periprocedural thromboembolic complications (n = 9) occurred more frequently in patients who were determined by all 3 methods to be clopidogrel resistant. The difference was most pronounced with light transmission aggregometry (complication rates, 14.4% clopidogrel-resistant patients] vs 3.7% clopidogrel-responsive patients]). Sensitivity and specificity rates of clopidogrel resistance in relation to embolic complications were, respectively, 78% and 55% for light transmission aggregometry, 67% and 51% for VerifyNow, and 44% and 67% for the Multiplate.CONCLUSIONS:Clopidogrel resistance is a frequent finding in patients who undergo neurovascular stent placement. The correlations among the different testing methods are only modest and differ considerably. Light transmission aggregometry results seem to correlate with thromboembolic complications more accurately than with VerifyNow and Multiplate point-of-care methods.

In neurovascular procedures, especially the placement of a stent into an extracranial or intracranial artery, clopidogrel resistance is associated with an increased risk of thromboembolic complications.^1–5 In elective neurovascular stent placement, preprocedural testing of platelet inhibition is increasingly performed to identify patients with clopidogrel resistance. However, test result standards for clopidogrel resistance have not been established, and strong clinical evidence that supports the idea that the results of such tests definitively alter clinical outcomes is still lacking. Light transmission aggregometry (LTA) is considered the criterion-standard test method, but standard values have not yet been established. LTA requires a preparation time of 2 hours, whereas point-of-care methods such as the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) and impedance aggregometry using a Multiplate analyzer (Dynabyte, Munich, Germany) offer periprocedural test results within minutes in the operating suite.⁶A study comparing LTA with point-of-care measurements in percutaneous coronary intervention has shown only modest agreement among the different tests.⁷ In neurovascular procedures, clopidogrel resistance has been investigated with various methods. However, a comparison of different test methods to determine the correlation of their results with the occurrence of embolic complications has not yet been performed in the clinical context of neurovascular stent placement.The purpose of this study was to determine the correlation of platelet inhibition with clopidogrel according to 3 different testing methods and the association of clopidogrel resistance with thromboembolic complications in elective neurovascular stent placement.